Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Lysosomal-associated transmembrane protein 4B

Gene

LAPTM4B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for optimal lysosomal function (PubMed:21224396). Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation (PubMed:25588945). Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation (PubMed:25998567). Plays a role as negative regulator of TGFB1 production in regulatory T cells (PubMed:26126825). Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways (PubMed:26280656).5 Publications

GO - Molecular functioni

  • ceramide binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • phosphatidylinositol bisphosphate binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • endosome organization Source: UniProtKB
  • endosome transport via multivesicular body sorting pathway Source: UniProtKB
  • negative regulation of lysosomal protein catabolic process Source: UniProtKB
  • negative regulation of transforming growth factor beta1 production Source: UniProtKB
  • regulation of lysosomal membrane permeability Source: UniProtKB
  • regulation of lysosome organization Source: UniProtKB

Keywordsi

Biological processTransport

Protein family/group databases

TCDBi2.A.74.1.3. the 4 tms multidrug endosomal transporter (met) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Lysosomal-associated transmembrane protein 4BCurated
Alternative name(s):
Lysosome-associated transmembrane protein 4-beta1 Publication
Gene namesi
Name:LAPTM4BImported
ORF Names:PSEC0001
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104341.16.
HGNCiHGNC:13646. LAPTM4B.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei170 – 190HelicalSequence analysisAdd BLAST21
Transmembranei216 – 236HelicalSequence analysisAdd BLAST21
Transmembranei244 – 264HelicalSequence analysisAdd BLAST21
Transmembranei297 – 317HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi349P → A: Abolishes binding to NEDD4; when associated with A-365. Increases localization to cell membrane; when associated with A-365. Retains association with HGS and enhances PIP5K1C interaction; when associated with A-365. Does not affect EGFR degradation; when associated with A-365. 2 Publications1
Mutagenesisi365P → A: Abolishes binding to NEDD4; when associated with A-349. Increases localization to cell membrane; when associated with A-349. Retains association with HGS and enhances PIP5K1C interaction; when associated with A-349. Does not affect EGFR degradation; when associated with A-349. 2 Publications1

Organism-specific databases

DisGeNETi55353.
OpenTargetsiENSG00000104341.
PharmGKBiPA128395785.

Polymorphism and mutation databases

BioMutaiLAPTM4B.
DMDMi74714056.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002497211 – 370Lysosomal-associated transmembrane protein 4BAdd BLAST370

Post-translational modificationi

Undergoes proteolytic cleavage following delivery to the lysosomes.1 Publication
Ubiquitinated by NEDD4.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ86VI4.
PaxDbiQ86VI4.
PeptideAtlasiQ86VI4.
PRIDEiQ86VI4.

PTM databases

iPTMnetiQ86VI4.
PhosphoSitePlusiQ86VI4.

Expressioni

Gene expression databases

BgeeiENSG00000104341.
CleanExiHS_LAPTM4B.
ExpressionAtlasiQ86VI4. baseline and differential.
GenevisibleiQ86VI4. HS.

Organism-specific databases

HPAiCAB020782.
HPA068830.

Interactioni

Subunit structurei

Homooligomer; upon reaching the lysosomes (PubMed:21224396). Interacts with MCOLN1 (PubMed:21224396). Interacts with NEDD4; may play a role in the lysosomal sorting of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of EGFR degradation (PubMed:22096579, PubMed:25588945). Interacts with PIP5K1C; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C (PubMed:25588945). Interacts with HGS; promotes HGS ubiquitination (PubMed:25588945). Interacts with SNX5 (PubMed:25588945). Interacts with SLC3A2 AND SLC7A5; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567). Interacts with LRRC32; decreases TGFB1 production in regulatory T cells (PubMed:26126825). Interacts with BECN1; competes with EGFR for LAPTM4B binding; regulates EGFR activity (PubMed:28479384). Interacts with EGFR; positively correlates with EGFR activation (PubMed:28479384).6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120633. 19 interactors.
IntActiQ86VI4. 11 interactors.
MINTiMINT-4726487.
STRINGi9606.ENSP00000402301.

Structurei

3D structure databases

ProteinModelPortaliQ86VI4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni349 – 365Required for NEDD4 interaction1 PublicationAdd BLAST17

Sequence similaritiesi

Belongs to the LAPTM4/LAPTM5 transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGWG. Eukaryota.
ENOG4111K1Z. LUCA.
GeneTreeiENSGT00390000013359.
HOGENOMiHOG000007698.
HOVERGENiHBG000908.
InParanoidiQ86VI4.
KOiK12387.
OMAiMSTNNMC.
OrthoDBiEOG091G0MA5.
PhylomeDBiQ86VI4.
TreeFamiTF330843.

Family and domain databases

InterProiView protein in InterPro
IPR004687. LAPTM4/5.
IPR018401. Lysosomal-assoc_TM_prot4B.
PANTHERiPTHR12479:SF6. PTHR12479:SF6. 1 hit.
PfamiView protein in Pfam
PF03821. Mtp. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86VI4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELHERPDER RKARTSTQGR LGDWRRVHAD GFTHRVLGAP AAAWSSSSWL
60 70 80 90 100
EPAMTSRTRV TWPSPPRPLP VPAAAAVAFG AKGTDPAEAR SSRGIEEAGP
110 120 130 140 150
RAHGRAGREP ERRRSRQQRR GGLQARRSTL LKTCARARAT APGAMKMVAP
160 170 180 190 200
WTRFYSNSCC LCCHVRTGTI LLGVWYLIIN AVVLLILLSA LADPDQYNFS
210 220 230 240 250
SSELGGDFEF MDDANMCIAI AISLLMILIC AMATYGAYKQ RAAWIIPFFC
260 270 280 290 300
YQIFDFALNM LVAITVLIYP NSIQEYIRQL PPNFPYRDDV MSVNPTCLVL
310 320 330 340 350
IILLFISIIL TFKGYLISCV WNCYRYINGR NSSDVLVYVT SNDTTVLLPP
360 370
YDDATVNGAA KEPPPPYVSA
Length:370
Mass (Da):41,146
Last modified:June 1, 2003 - v1
Checksum:iA6C04BFCB8B26EC9
GO
Isoform 2 (identifier: Q86VI4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.

Show »
Length:226
Mass (Da):25,419
Checksum:iA3156D2F2C0DCF0B
GO
Isoform 3 (identifier: Q86VI4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: Missing.

Show »
Length:317
Mass (Da):35,123
Checksum:i4E93093E066BE948
GO

Sequence cautioni

The sequence CAB66876 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti138R → S in AAH38117 (PubMed:15489334).Curated1
Sequence conflicti232M → T in AAH38117 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0205441 – 144Missing in isoform 2. 2 PublicationsAdd BLAST144
Alternative sequenceiVSP_0205451 – 53Missing in isoform 3. 4 PublicationsAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527412 mRNA. Translation: AAP14034.1.
AY057051 mRNA. Translation: AAL17908.2.
AF317417 mRNA. Translation: AAK69595.1.
AY261384 mRNA. Translation: AAO84265.1.
AK075326 mRNA. Translation: BAC11549.1.
AL136942 mRNA. Translation: CAB66876.2. Different initiation.
BC014129 mRNA. Translation: AAH14129.1.
BC031021 mRNA. Translation: AAH31021.1.
BC038117 mRNA. Translation: AAH38117.1.
CCDSiCCDS6275.1. [Q86VI4-3]
RefSeqiNP_060877.3. NM_018407.4. [Q86VI4-3]
UniGeneiHs.492314.

Genome annotation databases

EnsembliENST00000445593; ENSP00000402301; ENSG00000104341. [Q86VI4-3]
ENST00000521545; ENSP00000428409; ENSG00000104341. [Q86VI4-2]
ENST00000619747; ENSP00000482533; ENSG00000104341. [Q86VI4-3]
GeneIDi55353.
KEGGihsa:55353.
UCSCiuc003yia.4. human. [Q86VI4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiLAP4B_HUMAN
AccessioniPrimary (citable) accession number: Q86VI4
Secondary accession number(s): Q3ZCV5
, Q7L909, Q86VH8, Q9H060
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: June 1, 2003
Last modified: October 25, 2017
This is version 109 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families